A Tailor-Made Cancer Treatment Is Wowing Wall Street.

http://www.bloomberg.com/news/2014-12-19/juno-joins-bespoke-cancer-treatment-frenzy-as-questions-linger.html

It’s a cancer therapy straight out of Greek mythology, bespoke medicine with astonishing results in the smallest and sickest of patients.

The treatment, called a chimeric antigen receptor, or CAR for short, has captured the attention of the biggest drug companies and become a hotbed for biotechnology startups. A medical amalgam like the chimera in Homer’s “Iliad” -- a fire-breathing monster with a lion’s head, a goat’s body and a snake’s tail -- it may offer the best chance for patients like toddler Greta Oberhofer to beat acute lymphoblastic leukemia.

Investors have poured money into these firms, including Seattle-based Juno Therapeutics Inc., which ended its first day of trading today with a $2.7 billion valuation, leaping 46 percent above its price in an initial public offering. Yet therapies like Juno’s have only been tried on a couple of hundred patients, and commercializing a tailor-made medicine for the masses is a daunting task.

CARs are engineered T-cells, modified versions of the assassins the body normally deploys to identify and wipe out infected or abnormal cells. The human-made versions are produced by inserting a gene sequence into a T-cell, which allows the T-cell to recognize the tumors and attack them. Children who relapse after treatment for ALL, the most common childhood leukemia, have some of the most dramatic responses, with early signs of the cancer disappearing in up to 90 percent of them.

Juno’s Debut

Similarly stunning results have drawn some of the biggest pharmaceutical companies -- Novartis AG (NOVN), Pfizer Inc. (PFE), and Johnson & Johnson (JNJ) -- into the therapy, competing neck-and-neck with startup firms like Juno and Bellicum Pharmaceuticals Inc., which went public earlier this week, pricing at $19 a share, beyond the company’s expected range of $15 to $17.

Juno shot up to $35 today after its shares were priced at $24 last night to raise more than $200 million.

Kite Pharma Inc. (KITE), which went public in June, reported in August that 12 out of 13 patients with advanced B-cell lymphoma responded to its CAR treatment. Eight of the patients achieved complete remission.

“Every pharmaceutical company is jumping in because they are afraid to fall behind,” said Elizabeth Krutoholow, an analyst for Bloomberg Intelligence in New York. “The potential is there and they want to be involved in some way so they can catch up” if the field takes off, she said. “You have to get in while the iron is hot.”

The market for the treatments is small, since the treatment hasn’t yet been adapted for solid tumors, which account for more than 90 percent of the cancer population. In blood cancers like leukemia, the targets for CARs are found on a B cell, an antibody-making agent that people can live without at least temporarily. The targets on solid tumors, on the other hand, are also found on other healthy cells that patients would die without.

Then there are side effects, which can be deadly. Not everyone is as lucky as Greta, who tolerated the treatment well. The therapies can push the immune system into overdrive as they kill cancerous cells, causing a potentially fatal immune reaction called a cytokine storm. Juno noted that 18 percent of 28 adult patients in one of its trials experienced severe cytokine release syndrome, and two died. At least three patients have died from the condition in early Novartis trials, though researchers now treat patients with drugs that can calm the overactive immune system.

Blunt Tools

CAR also offers a tantalizing way to reduce the need for chemotherapy, radiation and bone marrow transplants -- blunt tools intended to wipe out cancer but often with toxic side effects, Lee said. More than one in four patients has significant, chronic side effects from standard chemotherapy, he said. As many as one in 10 die from a bone marrow transplant. Chemotherapy must be injected into the spinal cord to kill off any hiding tumor cells, which can damage everything from brain function and IQ to height.

While some patients have remained in complete remission for several years, it’s too soon to say they are cured, said Dario Campana, director of immunopathology at the National University ofSingapore and an early leader in the field. Some patients have relapsed on therapy, with tests showing the cancer no longer expressed proteins the CAR targeted, he said.

“I’ve been looking at leukemic cells for a long time and I’ve never seen that,” he said. “The tumors have a way to escape this type of therapy. It doesn’t happen regularly, but it does happen.”

CARs are still in their infancy, and the technology is evolving rapidly. “There is a tremendous amount of refinement going on,” said Michael Jensen, who ran the first CAR clinical trial in 1996.

Current-generation T-cells are the medical equivalent of a Model T Ford, said Jensen, director of thecBen Towne Center for Childhood Cancer at Seattle Children’s Research Center and a scientific founder at Juno. The cells will become safer and more effective as more funding pours in and research heats up, he said. “The Teslas are coming.”

Juno Therapeutics Inc. executives, employees, and their families gather for a photograph during the company's initial public offering at the Nasdaq MarketSite in New York, U.S., on Friday, Dec. 19, 2014. Juno Therapeutics Inc. ended its first day of trading today with a $2.7 billion valuation, leaping 46 percent above its price in an initial public offering.